The present invention relates to a pain sensory nerve stimulation apparatus which, with respect to sharp or first pain produced by stimulation of Aδ fibers and dull or second pain produced by stimulation of C fibers, can stimulate C fibers selectively.
In order to selectively evoke pain sensations by electrical stimulation, an electrode disclosed in WO2006/059430 has been developed. According to the electrode, it is possible to stimulate Aδ fibers (see FIG. 4 of WO2006/059430).
By contrast, in order to detect disorders of the peripheral nerve at its early stages that is one of the three major complications of diabetes mellitus, a method by which C fibers are selectively stimulated and responses to the stimulation are measured is highly requested. This is based on that C fibers have a nerve diameter of 0.4 to 1.2 μm, Aδ fibers have a diameter of 2 to 5 μm, and Aβ fibers which are connected to mechanoreceptors relating to touch pressure sensations, have a diameter of 5 to 12 μm, and that a peripheral nervous disorder often begins from small fibers. When it is possible to stimulate C fibers which are smaller than Aδ fibers that can be stimulated by the electrode disclosed in WO2006/059430, therefore, development of a nervous disorder can be known earlier, thereby largely contributing to knowing of progression of and adequate control of a diabetic nervous disorder. In a related-art technique of selective stimulating C fibers, a laser apparatus is used. In the case where a laser apparatus is used, however, large-scale testing equipment and facility are required, and the size, cost, and complexity of the apparatus are increased to cause a problem of versatility. The accuracy of C fiber stimulation by laser beams has not yet reached to a satisfactory level, and the probability of C fiber stimulation is low. Therefore, a laser apparatus has not been used in a clinical application.
Also in WO2006/059430, when stimulation is applied while a needle terminal of the stimulation electrode is set as a cathode and the surrounding electrode is set as a anode, it is possible to selectively stimulate Aδ fibers, but C fibers cannot be selectively stimulated.
In the field of the art, a related-art technique in which electrical stimulation of the negative polarity is applied to a stimulus-intended electrode attached to a desired stimulation portion, and the positive polarity is applied to a terminal electrode is usually employed because excitation of peripheral nerves is generated immediately below a stimulation electrode of the negative polarity. Also WO2006/059430 discloses that stimulation is applied while the needle electrode of the stimulation electrode is set as a cathode and the surrounding electrode is set as a anode, so that Aδ fibers can be selectively stimulated. However, it is well known in the field that, even when the electrical polarity is inverted, the inversion exerts no effect or influence on nerve stimulation from the skin surface which is used in a measurement of the somatosensory evoked potentials (SEPs) (see FIG. 10).
A related-art apparatus which automatically measures in an electrophysiologic or quantitative manner the electrical current perceptive threshold and the algestic tolerant threshold is known (see U.S. Pat. No. 5,806,522). In the related-art apparatus, stimulation is applied by using a sine wave, and C fibers, Aδ fibers, and Aβ fibers are most responsive to stimulation of frequencies of 5 Hz, 250 Hz, and 2,000 Hz, respectively. U.S. Pat. No. 5,806,522 does not disclose a technique in which C fibers, Aδ fibers, and Aβ fibers can be independently stimulated. In the related-art apparatus, stimulation due to a sine wave is required. Therefore, the related-art apparatus is complicated in structure for producing and controlling stimulation, as compared with the case where stimulation is applied by a pulse wave which is typified by a square wave.
The related-art apparatus disclosed in U.S. Pat. No. 5,806,522 uses a surface electrode, and hence the stimulation intensity to be applied is larger than the case where an electrode is inserted into the skin. In stimulation of small fibers such as C fibers, namely, there is a large possibility that also other nerve fibers such as tactile fibers are stimulated. Therefore, it is considered that selective stimulation of C fibers is difficult. Since stimulation due to a sine wave is applied, stimulation for 3 seconds must be applied two times in stimulation of C fibers (see Columns 8 and 9 of U.S. Pat. No. 5,806,522). During the measurement, the subject suffers from pain. Stimulation of C fibers can be known by calculating the conduction velocity by use of SEPs. In view of the fact that the conduction velocity in nerve fibers is about several m/s, when stimulation is performed for several seconds as in the related-art apparatus disclosed in U.S. Pat. No. 5,806,522, responses to the stimulation cannot be obtained, therefore, it is considered that identification of which nerve fibers are stimulated is impossible.
Japanese Patent No. 3,543,097 discloses a related-art apparatus in which specific tactile sensory receptors are selectively stimulated by using a surface electrode without evoking pain sensations. This related-art apparatus is effective in stimulating the tactile sensations. Since the surface electrode is used, however, the stimulation intensity is as large as about 2 mA as described before. Furthermore, Aδ fibers and C fibers which relate to the pain sensations are small fibers, and hence stimulation is hardly performed. In the related-art apparatus disclosed in Japanese Patent No. 3,543,097, therefore, it is impossible to selectively stimulate Aδ fibers and C fibers. The related-art apparatus disclosed in Japanese Patent No. 3,543,097 has a further problem in that a complex process such as a weighted change is required in selective stimulation of receptors.
In usual electrical stimulation, excitation is more easily caused in the sequence of Aβ fibers, Aδ fibers, and C fibers. Namely, electrical stimulation is more easily performed on thickly myelinated fibers, and excitation due to electrical stimulation most hardly occurs in C fibers that are small in diameter and unmyelinated. Therefore, stimulation of C fibers without affecting other fibers has been very difficult.